RT Journal Article SR Electronic T1 18F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1094 OP 1099 DO 10.2967/jnumed.116.188896 VO 58 IS 7 A1 Lohrke, Jessica A1 Siebeneicher, Holger A1 Berger, Markus A1 Reinhardt, Michael A1 Berndt, Mathias A1 Mueller, Andre A1 Zerna, Marion A1 Koglin, Norman A1 Oden, Felix A1 Bauser, Marcus A1 Friebe, Matthias A1 Dinkelborg, Ludger M. A1 Huetter, Joachim A1 Stephens, Andrew W. YR 2017 UL http://jnm.snmjournals.org/content/58/7/1094.abstract AB Thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and pulmonary embolism are major causes of morbidity and mortality worldwide. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the key receptor involved in platelet aggregation and is a validated target for therapeutic approaches and diagnostic imaging. The aim of this study was to develop and characterize a specific small-molecule tracer for PET imaging that binds with high affinity to GPIIb/IIIa receptors and has suitable pharmacokinetic properties to overcome limitations of previous approaches. Methods: Binding of 18F-GP1 to GPIIb/IIIa receptors was investigated in competition binding assays and autoradiography using a fresh cardiac thrombus from an explanted human heart. The clot-to-blood ratio for 18F-GP1 was investigated by an in vitro blood flow model. Biodistribution and thrombus detection was investigated in cynomolgus monkeys after insertion of a roughened catheter into either the vena cava or the aorta. Results: 18F-GP1 is an 18F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of 18F-GP1 to GPIIb/IIIa was 20 nM. 18F-GP1 bound to thrombi with a mean clot-to-blood ratio of 95. Binding was specific and can be displaced by excess nonradioactive derivative. Binding was not affected by anticoagulants such as aspirin or heparin. 18F-GP1 showed rapid blood clearance and a low background after intravenous injection in cynomolgus monkeys. Small arterial, venous thrombi, thrombotic depositions on damaged endothelial surface, and small cerebral emboli were detected in vivo by PET imaging. Conclusions: 18F-GP1 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics, 18F-GP1 is currently being investigated in a human clinical study.